Dissociating orexin-dependent and -independent functions of orexin neurons using novel Orexin-Flp knock-in mice.
cataplexy
chemogenetics
electrophysiology
flippase recombinase
mouse
neuroscience
orexin/hypocretin
sleep/wakefulness
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
04 06 2019
04 06 2019
Historique:
received:
06
01
2019
accepted:
09
05
2019
entrez:
5
6
2019
pubmed:
5
6
2019
medline:
25
2
2020
Statut:
epublish
Résumé
Uninterrupted arousal is important for survival during threatening situations. Activation of orexin/hypocretin neurons is implicated in sustained arousal. However, orexin neurons produce and release orexin as well as several co-transmitters including dynorphin and glutamate. To disambiguate orexin-dependent and -independent physiological functions of orexin neurons, we generated a novel Orexin-flippase (Flp) knock-in mouse line. Crossing with Flp-reporter or Cre-expressing mice showed gene expression exclusively in orexin neurons. Histological studies confirmed that orexin was knock-out in homozygous mice. Orexin neurons without orexin showed altered electrophysiological properties, as well as received decreased glutamatergic inputs. Selective chemogenetic activation revealed that both orexin and co-transmitters functioned to increase wakefulness, however, orexin was indispensable to promote sustained arousal. Surprisingly, such activation increased the total time spent in cataplexy. Taken together, orexin is essential to maintain basic membrane properties and input-output computation of orexin neurons, as well as to exert awake-sustaining aptitude of orexin neurons.
Identifiants
pubmed: 31159922
doi: 10.7554/eLife.44927
pii: 44927
pmc: PMC6548533
doi:
pii:
Substances chimiques
Orexins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Science and Technology Agency
ID : JPMJCR1656
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science, and Technology
ID : 26293046
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 26640041
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 16H01271
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 15H01428
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 18KK0223
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 19H05016
Pays : International
Informations de copyright
© 2019, Chowdhury et al.
Déclaration de conflit d'intérêts
SC, CH, SI, AI, MK, TK, HB, II, MA, KS, AY No competing interests declared
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